tbuckley/cabot-search huggingface dataset:
Modular Titratable Polypills for Personalized Medicine and Simplification of Complex Medication Regimens
Authors: Christina Karavasili, Sahab Babaee, Shruti Kutty, Jacqueline N. Chu, Seokkee Min, Nina Fitzgerald, Joshua Morimoto, Nicoletta Inverardi, Giovanni Traverso
Journal: Advanced Healthcare Materials (2023)

Simplification of complex medication regimens in polypharmacy positively contributes to treatment adherence and cost-effective improved health outcomes. Even though fixed dose combination (FDC) drug products are the only currently available single dose poly-pill regimens, the lack of flexibility in dose adjustment of a single drug in the combination limits their efficacy. To fill the existing gap in drug dose personalization and simplification of complex medication regimens commonly encountered in the treatment of cardiovascular disease, tuberculosis, and tapering of corticosteroid therapy, a modular titratable polypill approach that simultaneously addresses both aspects is proposed. The polypill consists of modular units that contain different drugs at incremental or decremental doses to be assembled in a single titratable polypill at the required dose for each drug through a stacking or interlocking process. The variable dose (VD) modular tablets are subjected to quality control tests and found to comply to pharmacopeia's acceptance criteria and requirements specified in the respective drug monographs. A cost-effectiveness analysis is conducted supporting the VD strategy as cost-effective compared to the FDC strategy and more effective and less expensive than standard of care. The VD approach stands to enable pill burden reduction, ease of administration, enhancement of treatment adherence, and potential cost-saving benefits.
Long-term outcomes of aortic valve replacement in dialysis patients – a nationwide retrospective cohort study
Authors: Hsun-Yi Fu, Ting-Chuan Wang, Chih-Hsien Wang, Nai-Kuan Chou, I-Hui Wu, Ron-Bin Hsu, Shu-Chien Huang, Hsi-Yu Yu, Yih-Sharng Chen, Nai-Hsin Chi
Journal: International Journal of Surgery (2023)

Improved durability of modern biologic prostheses and growing experience with the transcatheter valve-in-valve technique have contributed to a substantial increase in the use of bioprostheses in younger patients. However, discussion of prosthetic valve selection in dialysis patients remains scarce as the guidelines are updated. This study aims to compare long-term outcomes between propensity score-matched cohorts of dialysis patients who underwent primary aortic valve replacement with a mechanical prosthesis or a bioprosthesis.Longitudinal data of dialysis patients who underwent primary aortic valve replacement between 1 January 2001 and 31 December 2018, were retrieved from the National Health Insurance Research Database.A total of 891 eligible patients were identified, of whom 243 ideally matched pairs of patients were analyzed. There was no significant difference in all-cause mortality (hazard ratio 1.11, 95% CI: 0.88-1.40) or the incidence of major adverse prosthesis-related events between the two groups (hazard ratio 1.03, 95% CI: 0.84-1.25). In patients younger than 50 years of age, using a mechanical prosthesis was associated with a significantly longer survival time across 10 years of follow-up than using a bioprosthesis (restricted mean survival time) at 10 years: 7.24 (95% CI: 6.33-8.14) years for mechanical prosthesis versus 5.25 (95% CI: 4.25-6.25) years for bioprosthesis, restricted mean survival time difference 1.99 years, 95% CI: -3.34 to -0.64).A 2-year survival gain in favor of mechanical prostheses was identified in dialysis patients younger than 50 years. The authors suggest mechanical prostheses for aortic valve replacement in these younger patients.
Pediatric Mental Health Hospitalizations at US Acute Care Hospitals
Authors: Andrew D. Carlo, Clare McNutt, Hani Talebi
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The phospholipase effector Tle1 <sup>Vc</sup> promotes <i>Vibrio cholerae</i> virulence by killing competitors and impacting gene expression
Authors: Ming Liu, Heng Wang, Ying Liu, Miao Tian, Zhao Wang, Run-Dong Shu, Meng-Yu Zhao, Wei-Di Chen, Hao Wang, Hui Wang, Yang Fu
Journal: Gut Microbes (2023)

Vibrio cholerae utilizes the Type VI secretion system (T6SS) to gain an advantage in interbacterial competition by delivering anti-prokaryotic effectors in a contact-dependent manner. However, the impact of T6SS and its secreted effectors on physiological behavior remains poorly understood. In this study, we present Tle1Vc, a phospholipase effector in atypical pathogenic V. cholerae E1 that is secreted by T6SS via its interaction with VgrG1E1. Tle1Vc contains a DUF2235 domain and belongs to the Tle1 (type VI lipase effector) family. Bacterial toxicity assays, lipase activity assays and site-directed mutagenesis revealed that Tle1Vc possessed phospholipase A1 activity and phospholipase A2 activity, and that Tle1Vc-induced toxicity required a serine residue (S356) and two aspartic acid residues (D417 and D496). Cells intoxication with Tle1Vc lead to membrane depolarization and alter membrane permeability. Tli1tox-, a cognate immunity protein, directly interacts with Tle1Vc to neutralize its toxicity. Moreover, Tle1Vc can kill multiple microorganisms by T6SS and promote in vivo fitness of V. cholerae through mediating antibacterial activity. Tle1Vc induces bacterial motility by increasing the expression of flagellar-related genes independently of functional T6SS and the tit-for-tat (TFT) response, where Pseudomonas aeruginosa uses its T6SS-H1 cluster to counterattack other offensive attackers. Our study also demonstrated that the physical puncture of E1 T6SS can induce a moderate TFT response, which is essential to the Tle1Vc-mediated strong TFT response, maximizing effector functions. Overall, our study characterized the antibacterial mechanism of phospholipase effector Tle1Vc and its multiple physiological significance.
Identification and initial validation of maximal tumor area as a novel prognostic factor for overall and disease-free survival in patients with resectable colon cancer: a retrospective study
Authors: Fei-Long Ning, Wan-Jie Gu, Lin-Zheng Dai, Wan-Ying Du, Yong-Ji Zeng, Jia-Kui Zhang, Masanobu Abe, Yan-Long Liu, Rui Zhang, Chun-Dong Zhang
Journal: International Journal of Surgery (2023)

The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer.This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along with the prognostic discrimination between the tumor-node-metastasis (TNM) staging system and other prognostic models. Two-sample Wilcoxon tests were carried out to identify significant differences between the two iAUCs. A two-sided P <0.05 was considered statistically significant.A total of 3051 colon cancer patients were included in the training cohort and 872 patients in the validation cohort. Tumor area, age, differentiation, T stage, and N stage were independent prognostic factors for both OS and DFS in the training cohort. Tumor area had a better OS and DFS prognostic discrimination characteristics than T stage, maximal tumor diameter, differentiation, tumor location, and number of retrieved lymph nodes. The novel prognostic model of T stage + N stage + tumor area (iAUC for OS, 0.714, P <0.001; iAUC for DFS, 0.694, P <0.001) showed a better prognostic discrimination than the TNM staging system (T stage + N stage; iAUC for OS, 0.664; iAUC for DFS, 0.658). Similar results were observed in an independent validation cohort.Tumor area was identified as an independent prognostic factor for both OS and DFS in curable colon cancer patients, and in cases with an adequate number of retrieved lymph nodes. The novel prognostic model of combining T stage, N stage, and tumor area may be an alternative to the current TNM staging system.
Optimizing treatment of primary biliary cholangitis: Is good, good enough?
Authors: Christopher L. Bowlus, Cynthia Levy
Journal: Hepatology (2023)

1University of California Davis, Sacramento, CA, USA 2Schiff Center for Liver Disease and Division of Gastroenterology and Hepatology, University of Miami, Miami, FL, USA List of Abbreviations: ALP, alkaline phosphatase; LSM, liver stiffness measurement; LT, liver transplantation; OCA, obeticholic acid; PBC, primary biliary cholangitis; UDCA, ursodeoxycholic acid; ULN, upper limit of normal. Editorial to HEPATOLOGY: HEP-23-480.R2 "Adequate versus deep response to UDCA in PBC: to what extent and under what conditions is normal ALP level associated with complication-free survival gain?" Correspondence Christopher L. Bowlus, Division of Gastroenterology and Hepatology, UC Davis Health, 4150 V Street, PSSB 3500, Sacramento, CA 95616. Email: [email protected]
Treating Coronary Artery Disease With Treat-to-Target or High-Intensity Statin—Reply
Authors: Sung-Jin Hong, Yong-Joon Lee, Myeong-Ki Hong
Journal: JAMA (2023)

In Reply We appreciate Dr Kawada’s comments about our study, which demonstrated that a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization.1
Nepenthe
Authors: Scott C. Biggerstaff
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Ratio of Key Metabolic Transcripts Is a Predictive Biomarker of Breast Cancer Metastasis to the Lung
Authors: Deepti Mathur, Chen Liao, Wendy Lin, Alessandro La Ferlita, Salvatore Alaimo, Samuel Taylor, Yi Zhong, Christine Iacobuzio-Donahue, Alfredo Ferro, Joao B. Xavier
Journal: Cancer Research (2023)

Abstract Understanding the rewired metabolism underlying organ-specific metastasis in breast cancer could help identify strategies to improve the treatment and prevention of metastatic disease. Here, we used a systems biology approach to compare metabolic fluxes used by parental breast cancer cells and their brain- and lung-homing derivatives. Divergent lineages had distinct, heritable metabolic fluxes. Lung-homing cells maintained high glycolytic flux despite low levels of glycolytic intermediates, constitutively activating a pathway sink into lactate. This strong Warburg effect was associated with a high ratio of lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) expression, which correlated with lung metastasis in patients with breast cancer. Although feature classification models trained on clinical characteristics alone were unable to predict tropism, the LDH/PDH ratio was a significant predictor of metastasis to the lung but not to other organs, independent of other transcriptomic signatures. High lactate efflux was also a trait in lung-homing metastatic pancreatic cancer cells, suggesting that lactate production may be a convergent phenotype in lung metastasis. Together, these analyses highlight the essential role that metabolism plays in organ-specific cancer metastasis and identify a putative biomarker for predicting lung metastasis in patients with breast cancer. Significance: Lung-homing metastatic breast cancer cells express an elevated ratio of lactate dehydrogenase to pyruvate dehydrogenase, indicating that ratios of specific metabolic gene transcripts have potential as metabolic biomarkers for predicting organ-specific metastasis.
Pediatric Mental Health Hospitalizations at US Acute Care Hospitals
Authors: Yin-Hsuan Chien, Nin-Chieh Hsu
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sodium-glucose cotransporter 2 inhibitor canagliflozin alleviates vascular calcification through suppression of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome
Authors: An Chen, Zirong Lan, Li Li, Luting Xie, Xiaoyu Liu, Xiulin Yang, Siyi Wang, Qingchun Liang, Qianqian Dong, Liyun Feng, Yining Li, Yuanzhi Ye, Mingwei Fu, Lihe Lu, Jianyun Yan
Journal: Cardiovascular Research (2023)

Vascular calcification (VC) is prevalent in pathological processes such as diabetes, chronic kidney disease (CKD), and atherosclerosis, but effective therapies are still lacking by far. Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, has been approved for the treatment of type 2 diabetes mellitus and exhibits beneficial effects against cardiovascular disease. However, the effect of CANA on VC remains unknown. In this study, we hypothesize that CANA protects against VC.Micro-computed tomography analysis and alizarin red staining revealed that CANA treatment prevented aortic calcification in CKD rats and in VitD3-overloaded mice. Moreover, CANA alleviated the calcification of rat and human arterial rings. Alizarin red staining revealed that calcification of rat and human vascular smooth muscle cells (VSMCs) was attenuated by CANA treatment and this phenomenon was confirmed by calcium content assay. In addition, CANA downregulated the expression of osteogenic differentiation markers Runx2 and BMP2. Of interest, qPCR and western blot analysis revealed that CANA downregulated the expression of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and the downstream signalling molecules Caspase-1 and IL-1β in VSMCs as well. Both NLRP3 inhibitor MCC950 and knockdown of NLRP3 by siRNA independently resulted in decreased calcification of VSMCs. By contrast, activation of NLRP3 exacerbated VSMC calcification, and this effect was prevented by the addition of CANA.Our study for the first time demonstrates that CANA exerts a protective effect on VC at least partially via suppressing the NLRP3 signalling pathway. Therefore, supplementation of CANA as well as inhibition of NLRP3 inflammasome presents a potential therapy for VC.
Folic Acid Supplementation to Prevent Neural Tube Defects
Authors: Michael J. Barry, Wanda K. Nicholson, Michael Silverstein, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Li Li, Gbenga Ogedegbe, Goutham Rao, John M. Ruiz, James Stevermer, Joel Tsevat, Sandra Millon Underwood, John B. Wong
Journal: JAMA (2023)

Importance Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube defects are caused by low folate levels in the body. Objective The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on the benefits and harms of folic acid supplementation. Population Persons who are planning to or could become pregnant. Evidence Assessment The USPSTF concludes that, for persons who are planning to or could become pregnant, there is high certainty that folic acid supplementation has a substantial net benefit to prevent neural tube defects in their offspring. Recommendation The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 μg) of folic acid. (A recommendation)
Litigation on kidney transplantation: 10-year experience from China
Authors: Qiyu He, Zhimin Tan, Liang Zhou
Journal: International Journal of Surgery (2023)

aDepartment of Urology, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China bDepartment of Anaesthesiology, West China Hospital of Sichuan University, Sichuan Province, Chengdu, 610041, China Qiyu He, Zhimin Tan, These authors have contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: West China Hospital of Sichuan University, CHINA. E-mail address: [email protected] (L. Zhou). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Reaffirming Recommendations for Folic Acid Supplementation
Authors: David B. Nelson, Catherine Y. Spong
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Perioperative ketamine administration to prevent delirium and neurocognitive disorders after surgery: a systematic review and meta-analysis
Authors: Fellous Souad, Baptiste Dubost, Amélie Cambriel, Marie-Pierre Bonnet, Franck Verdonk
Journal: International Journal of Surgery (2023)

Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect of perioperative ketamine on postoperative delirium and postoperative neurocognitive disorders (POND). Systematic review and meta-analysis including all randomized controlled trials investigating the effects of perioperative ketamine administration in adult patients compared to placebo or no intervention on postoperative delirium and/or POND between January 2007 and April 2022. Database searches were conducted in PubMed, Medline, Embase, Scopus, and Central. Random effects models were used to pool overall estimates. The GRADE approach was used to assess the quality of the evidence. From 1379 records screened, 14 randomized controlled trials with 1618 patients randomized met our inclusion criteria with a high level of consensus among reviewers, amongst whom 50% were at low-moderate risk of bias. There was no between-group difference in postoperative delirium [8 trials, 1265 patients, odds ratio (OR) 0.93, 95% CI (0.51-1.70), I2 =28%] and POND [5 trials, 494 patients, OR 0.52, 95% CI (0.15-1.80); I2 =78%]. There was no significant between-group difference in postoperative psychological adverse effects, level of pain, hospital length of stay, or mortality. Between-group subgroup analyses showed no difference in delirium or POND incidence according to surgical setting, ketamine dose, mode of administration, combination or not with other drug(s), and assessment timing or definition of cognitive disorders. Perioperative ketamine does not prevent postoperative delirium or POND. Significant study heterogeneity suggests that standardized measures for POND assessment and a specific focus on patients at high risk for POND should be used to improve the comparability of future studies.